title: Ligand-induced nuclear translocation of S1P(1) receptors mediates Cyr61 and CTGF transcription in endothelial cells.
abstract: Sphingosine-1-phosphate (S1P) receptor subtype 1 (S1P(1)), a G-protein coupled receptor (GPCR), regulates many biological activities of endothelial cells (ECs). In this report, we show that S1P(1) receptors are present in the nuclei of ECs by using various biochemical and microscopic techniques such as cellular fractionation, immunogold labeling, and confocal microscopic analysis. Live cell imaging showed that plasma membrane S1P(1) receptors are rapidly internalized and subsequently translocated to nuclear compartment upon S1P stimulation. Utilizing membrane biotinylation technique further supports the notion that nuclear S1P(1) receptors were internalized from plasma membrane S1P(1) after ligand treatment. Moreover, nuclear S1P(1) is able to regulate the transcription of Cyr61 and CTGF, two growth factors functionally important in the regulation of vasculature. Collectively, these data suggest a novel S1P-S1P(1) signaling axis present in the nuclear compartment of endothelial cells, which may regulate biological responses of endothelium.
authors.affiliation: Department of Microbiology and Immunology, Gheens Center on Aging, University of Louisville Health Sciences Center, Louisville, KY 40202, USA.
authors.forename: Rosendo
authors.initials: R
authors.lastname: Estrada
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Venkatakrishna R
authors.initials: VR
authors.lastname: Jala
authors.forename: Jen-Fu
authors.initials: JF
authors.lastname: Lee
authors.forename: Cheng-Yon
authors.initials: CY
authors.lastname: Lin
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gray
authors.forename: Bodduluri
authors.initials: B
authors.lastname: Haribabu
authors.forename: Menq-Jer
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D021581:Active Transport, Cell Nucleus; D002462:Cell Membrane; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D055515:Cysteine-Rich Protein 61 / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular; D006801:Humans; D008024:Ligands; D008246:Lysophospholipids / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C501848:CCN1 protein, human; C526317:CCN2 protein, human; D055515:Cysteine-Rich Protein 61; D008024:Ligands; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; D055513:Connective Tissue Growth Factor; C060506:sphingosine 1-phosphate; D013110:Sphingosine